Failure of the 1976 Swine Influenza Immunization Program

The swine flu immunization program is over. There was no epidemic and as of July 5, 1977, the U.S. Center for Disease Control (CDC) reported that about 45 million people had been vaccinated against swine influenza. The Center had originally hoped to immunize 210 million. There are two indications that the program failed, a direct one that can be recognized today and an indirect one that bears on future mass immunization campaigns. First, the goal of vaccinating more than 210 million Americans did not even come close to realization. The national program began October 1, 1976. It was halted December 16, 1976, because halted December 16, 1976, because about 200 people had come down with GuillainBarre syndrome, a very rare and usually temporary paralysis had come down with GuillainBarre syndrome,

H1N1 is an influenza virus. When it was first detected in 2009, it was called “swine flu” because the virus was similar to those found in pigs.  The World Health Organization declared a pandemic alert. A specialized flu vaccine, the swine flu H1N1 shot, was developed for persons of all ages: infants, adults, elderly and pregnant women. On August 10, 2010 WHO announced that the world is in a post-pandemic period. However, H1N1 is still circulating. The H1N1 strain is now included in the 2011-2012 seasonal flu vaccine.

Package Inserts: Influenza A (H1N1) 2009 Monovalent Vaccine (CSL Limited)

Influenza A (H1N1) 2009 Monovalent Vaccine (ID Biomedical Corporation of Quebec)

Influenza A (H1N1) 2009 Monovalent Vaccine (Novartis Vaccines and Diagnostics Limited)

Influenza A (H1N1) 2009 Monovalent Vaccine (Sanofi Pasteur, Inc.)

H1N1 Intranasal Vaccine

Influenza A (H1N1) 2009 Monovalent Vaccine (MedImmune LLC)

July 2019 – Social networks and the emergence of health inequalities following a medical advance: Examining prenatal H1N1 vaccination decisions “Our findings provide evidence that health decisions are shaped by individual resources as well as social capital available through network ties, offering a unique perspective of the ways that social networks contribute to producing, and potentially reproducing, unequal health.”

May 2019 – Change in risk for narcolepsy over time and impact of definition of onset date following vaccination with AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix) during the 2009 H1N1 influenza pandemic “With first symptom defining index date, the adjusted risk for narcolepsy in younger patients was increased 14 times during the first year after vaccination, three times elevated the second year, but with no detectable increased risk more than 2 years after vaccination exposure. Using the index date from the patient registry, the adjusted increase in risk was about seven times elevated for all three time intervals.”

April 2018 – Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis “In our paper, we show that the risk appears to be limited to only one vaccine (Pandemrix®). During the first year after vaccination, the relative risk of narcolepsy was increased 5 to 14-fold in children and adolescents and 2 to 7-fold in adults. The vaccine attributable risk in children and adolescents was around 1 per 18,400 vaccine doses. Studies from Finland and Sweden also appear to demonstrate an extended risk of narcolepsy into the second year following vaccination, but such conclusions should be interpreted with a word of caution due to possible biases. Benefits of immunization outweigh the risk of vaccination-associated narcolepsy, which remains a rare disease.

June 8, 2018 – Update: ACIP Recommendations for the Use of Quadrivalent Live Attenuated Influenza Vaccine (LAIV4) — United States, 2018–19 Influenza Season “During the 2016–17 and 2017–18 influenza seasons, the Advisory Committee on Immunization Practices (ACIP) recommended that LAIV4 not be used because of concerns about low effectiveness against influenza A(H1N1)pdm09-like viruses circulating in the United States during the 2013–14 and 2015–16 seasons. On February 21, 2018, ACIP recommended that LAIV4 be an option for influenza vaccination of persons for whom it is appropriate for the 2018–19 season. … “Data presented by the manufacturer indicated that the new LAIV4 influenza A(H1N1)pdm09-like virus, A/Slovenia/2903/2015, was shed by a higher proportion of children during days 4 through 7 following the first of 2 doses of vaccine.

October 9, 2017 – Hemagglutinin-specific CD4+ T-cell responses following 2009-pH1N1 inactivated split-vaccine inoculation in humans “In conclusion, our study indicates that HA-specific CD4+ T-cell responses can be primed by the inactivated 2009-pH1N1 vaccine, which may coordinate with the elicitation of antibody protection. These findings would benefit a better understanding of the immune protective mechanisms of the widely used inactivated 2009-pH1N1 vaccine.”

July 2017 – Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD65-induced immune response (full text) “Although the investigation of immune interference with combined vaccination and the assessment of immune responses to vaccinations are important parts of vaccine development, the possible interference of vaccines with autoantigen treatment in type 1 diabetes is a poorly explored field. According to our results, the reduced specific immune response to GAD65 in individuals with a shorter relative time between H1N1 and GAD-alum injections suggests that the powerful immunomodulatory effect of the adjuvant AS03 used in the Pandemrix vaccine might have affected the specific immune response induced by GAD-alum.”

June 2017 – Long-Term Persistence of Cell-Mediated and Humoral Responses to A(H1N1)pdm09 Influenza Virus Vaccines and the Role of the AS03 Adjuvant System in Adults during Two Randomized Controlled Trials “In previous trials, prior seasonal influenza vaccination and advancing age of the (adult) vaccinee were shown to be negative determinants of the humoral and/or cell-mediated immune (CMI) responses to A(H1N1)pdm09 vaccine.

May 25, 2017 – Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer’s view (full text) “A PASS was conducted in Quebec, Canada, a country where there was no signal, to investigate differences between the safety profiles of Arepanrix and Pandemrix and a potential class effect. The choice of Canada was also driven by lack of access to most European data sources; the fact that potential bias due to public and regulatory attention in Europe was marginal; and the opportunity of primary data collection and a H1N1 vaccination registry. The heterogeneity in risk estimates derived from the various methodological approaches in the Quebec study pointed to no strong evidence of an association between Arepanrix and narcolepsy. Challenges were inherent to the complex natural history of narcolepsy and the general inability to account for confounders. Based on the entirety of epidemiological data, narcolepsy is included in the RMP of all (AS03) pandemic influenza vaccines as an identified risk, with corresponding pharmacovigilance monitoring measures and an updated PI.”

May 3, 2017 – Bell’s palsy and influenza(H1N1)pdm09 containing vaccines: A self-controlled case series “We found an incidence rate of Bell’s palsy of 38.7 per 100,000 person years. Both acute respiratory infection (ARI) consultations and pregnancy were found to be confounders. When adjusted for seasonality, ARI consultations and pregnancies, the RI during the 42 days after vaccination with an influenza vaccine was 0.85 (95% CI: 0.72–1.01). The RI was similar during the 42 days following seasonal vaccine (0.96, 95%CI: 0.82–1.13) or pandemic vaccine (0.73, 95%CI: 0.47–1.12).”

April 11, 2017 – Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis “Through a comprehensive global systematic review and meta-analysis, we have identified that inactivated monovalent A(H1N1)pdm09 vaccines were effective in preventing laboratory-confirmed influenza illness and related hospitalization. In children, adjuvanted vaccines were more effective than unadjuvanted vaccines.”

• Potential conflicts of interest JSN-V-T declares funding for a 3-year PhD research fellowship from GlaxoSmithKline Biologicals SA which ended in 2014. In 2000–2001 he was an employee of SmithKline Beecham plc (now a part of the GlaxoSmithKline) and from 2002 to 2004 an employee of Aventis Pasteur MSD (now Sanofi Pasteur MSD), but has held no shares, share options or accrued pension rights in either company since 2005. He has given lectures (without fees or honoraria) at two scientific meetings of the European Scientific Working Group on Influenza (ESWI) in 2014 and 2015 for which travel expenses and accommodation were reimbursed). JSN-V-T’s brother was an employee of GlaxoSmithKline in an unrelated area until mid-2015.

• WB declares grants outside the submitted work from Abbott (pharmaceutical firm) for conference attendance and from Mylan (pharmaceutical firm) for an expert report.

April 4, 2017 – Narcolepsy and hypersomnia in Norwegian children and young adults following the influenza A(H1N1) 2009 pandemic (full text) “In summary, we confirm a statistically significant association between vaccination with Pandemrix and narcolepsy in complete population data. Although a slightly increased HR of narcolepsy and hypersomnia is seen after influenza infection, overall, the role of influenza in the development of narcolepsy and hypersomnia should be viewed with caution due to underreporting of influenza. However, it is remarkable that when both infection and vaccination are present, HRs are increased, suggesting a synergy. Thus, the HR for narcolepsy after vaccination may be inflated since many vaccinated subjects probably were infected before vaccination.”

February 2017 – Seropositivity of influenza A H1NI in mothers and infants following maternal vaccination with trivalent seasonal influenza vaccine after the 2009 pandemic ” (full text) “However, a higher baseline or prevaccination serum titer when the same antigen was used in consecutive years may result in hyporesponsiveness to repeated immunization in pregnant women. Trivalent inactivated influenza vaccination received at postpartum also exhibited hyporesponsiveness.

Vol. 56 2017 – Interstitial Pneumonia Associated with the Influenza Vaccine: A Report of Two Cases“Our search identified 9 cases (5 men and 4 women; mean age, 62.2 years; age range, 38-75 years) of influenza vaccine-induced interstitial pneumonia, including the present 2. Three were associated with a vaccine without the A(H1N1)pdm09-like antigen (6-8) and six with a monovalent influenza A(H1N1)pdm09 vaccine or a vaccine containing the A(H1N1)pdm09-like antigen.”

December 1, 2016 – Pathways to preterm birth: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data (full text) “In the case of preterm labor, while almost 100 studies were found based on the search terms preterm labor and immunization, only three of the articles mentioned preterm labor in the text of the articles, with only one reporting the incidence of preterm labor in the setting of an immunization. That paper reported that following administration of influenza A (H1N1) 2009 monovalent vaccine, 294 adverse events in pregnant women were reported to the Vaccine Adverse Event Reporting System; two women experienced preterm labor, or 1% of the immunized population in the United States. There was no description of the definition used for preterm labor in this study or the long-term outcomes of those pregnancies; overall, however, it was determined that preterm labor was not likely due to the immunization itself.”

December 1, 2016 – Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women (full text) “One of the conclusions of the workshop was that the data collected and presented from vaccine trials in both neonates and pregnant women should be harmonized. Similarly, at an international meeting on vaccination in pregnancy in 2012, it was noted that there were no widely accepted guidelines for data collection in studies of vaccination in pregnancy. This lack of harmonization was also evident when evaluating the studies conducted during the 2009–2010 H1N1 influenza pandemic, when vaccines were administered to large numbers of pregnant women worldwide.

October 1, 2016 – Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy “Narcolepsy with cataplexy (NC) is a chronic neurological disorder thought to result from an altered immune response based on a genetic predisposition coupled with environmental factors. Pandemrix vaccination has been reported to increase the risk of narcolepsy. We aimed at identifying other vaccines associated with the onset of narcolepsy.”

September 30, 2016 – Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States (full test) “These analyses suggest that the known increased susceptibility of the A/California/7/2009pdm09 LAIV strain to thermal degradation and potential exposure of some LAIV lots to heat during US distribution may explain the lack of VE observed with LAIV in 2013–2014 in the US. LAIV effectiveness against A/H1N1pdm09 strains was significantly associated with both vaccine shipping date and the outdoor temperatures to which lots could have been exposed during US distribution.”

August 24, 2016 – Antibody Responses to Influenza A H1N1 Vaccine Compared to the Circulating Strain in Influenza Vaccine Recipients during the 2013/2014 Season in North America “In IIV3 recipients, HAI and MN titers against H1N1-14 were significantly lower than against H1N1-09 (p < 0.0001 and 0.04, respectively). In LAIV4 recipients, only MN titers were significantly lower (p = 0.02) for H1N1-09 compared with H1N1-14. A combined analysis showed significantly lower HAI and MN titers for H1N1-14 compared with H1N1-09 (p = 0. 016 and 0.008, respectively). All 38 clinical isolates encoded the HA gene K166Q non-synonymous substitution; other non-synonymous substitutions were observed in <10% of the clinical isolates.”

August 19, 2016 – Unintentional administration of insulin instead of influenza vaccine: a case study and review of reports to US vaccine and drug safety monitoring systems “Investigation of the primary cluster incident revealed deviations from recommended practices for storage, handling, preparation, and administration of drugs and vaccines; the five cases were classified as highly suggestive of insulin and influenza vaccine mix-ups. Our search of CDC and FDA vaccine and drug safety monitoring databases identified an additional two highly suggestive and 15 suggestive cases, for a total of 22 cases (7 highly suggestive and 15 suggestive) during the 10-year study period.”

August 17, 2016 – Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009–2010 season in the active component U.S. military and civilians aged 17–44 years reported to the Vaccine Adverse Event Reporting System “Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain–Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million).

August 4, 2016 – Preexisting Antibody-Dependent Cellular Cytotoxicity–Activating Antibody Responses Are Stable Longitudinally and Cross-reactive Responses Are Not Boosted by Recent Influenza Exposure “However, little is known about the kinetics of these ADCC responses. We used retrospective serial blood samples from healthy donors to investigate this topic. All donors had ADCC responses against 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) and avian influenza A(H7N9) virus hemagglutinins (HAs) despite being seronegative for these viruses in standard hemagglutination inhibition and microneutralization serological assays. A(H1N1)pdm09 exposure did not boost ADCC responses specific for H7 HA antigens.”

August 3, 2016 – Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009 A/H1N1 Influenza Vaccination (full text) “In summary, during the second wave of the 2009 A/H1N1 influenza pandemic, we did not observe any reduction in rates of influenza or pneumonia among infants born to mothers who had received the monovalent pandemic vaccine during pregnancy compared with non-exposed infants. The limited infant follow-up time during the pandemic time period due to delayed availability of the pandemic vaccine illustrates the challenges of influenza immunization of pregnant women as a strategy to protect infants during a pandemic.”

June 19, 2016 – Acute flaccid myelitis in the United States – August – December 2014: Results of nation-wide surveillance “Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but one case was hospitalized; none died. CSF pleocytosis (>5 white blood cells/mm3) was common (81%). At CDC, one CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time PCR, although the specimen had >3,000 red blood cells/mm3.”…”There is some evidence to suggest that the nasal spray vaccine may not protect children against H1N1 viruses during the 2014-2015 season because the same H1N1 vaccine virus from the 2013-2014 vaccine is included in the 2014-2015 vaccine“…”Acute onset of limb weakness in children, CDC has been working with healthcare professionals and state and local health departments to investigate reports of children across the United States who developed a sudden onset of weakness in one or more arms or legs, MRI scans show an inflammation predominantly of the gray matter—nerve cells—in the spinal cord. This illness is now being referred to as acute flaccid myelitis. From August 2 to November 26, 2014, CDC has verified reports of 90 children in 32 states who developed acute flaccid myelitis that meets CDC’s case definition.” Comment: Mass campaigns usually start with fear.

May, 2016 – Anaphylaxis Following Immunization of Children and Adolescents in Germany. “Anaphylaxis occurred most frequently following administration of AS03 adjuvanted A/H1N1 pandemic influenza vaccine (n=8). The annual frequency of anaphylaxis after vaccination (excluding pandemic influenza vaccine as well as monovalent measles and rubella vaccines) was estimated to be 6.8 (95% CI: 6.1-10.9). The estimated incidence of anaphylaxis following administration of specific vaccines ranged from 0.4 to 127.6 cases per 1,000,000 doses administered.” Comment: AS03 is in the pipeline for a universal influenza vaccine.”

February 16, 2016 – Letters Maternal vaccination against H1N1 influenza and offspring mortality Concerns about study on maternal H1N1 influenza vaccination and offspring mortality (full text) “Thirdly, the authors defined the outcome as overall death, including stillbirth, early neonatal death, and death thereafter. The evaluation should have included other relevant outcomes, such as preterm birth, low birth weight small for gestational age, and spontaneous abortion, as previous studies have done. We would be interested to know whether it is possible to evaluate these other outcomes using this study’s database or external data on prenatal visits.”

2016 – Immunogenicity and Safety of Pandemic Influenza H5N1 Vaccines in Healthy Adults through Meta-Analysis (full text) “This analysis also included different types of adjuvants. Some reported AEs were mild to moderate and included fever, headache, and injection point pain. However, we could not determine specific reasons for these AEs. It should be noted that there was no evidence to prove the relationship between a higher dose and an increased risk of adverse events in the non-adjuvant group (Table 4). We concluded that the studied dosages of H5N1 AIV were well tolerated.”

August 6, 2015 – New Evidence Associates Narcolepsy with Pandemic Flu Vaccine “The researchers identified antibodies to a particular protein fragment contained in a piece of the virus used to make the Pandemrix vaccine. That fragment, part of the influenza nucleoprotein (NP), cross-reacted with human hypocretin receptor 2 (HCRT R2), which is involved in the sleep dysregulation observed in narcolepsy, they reported.”…”“The findings suggest that natural infections can trigger an autoimmune response that involves molecular mimicry” — a similarity between a vaccine antigen and a hypocretin-related structure in the brain, said S. Sohail Ahmed, MD, a rheumatologist and co-author of the study with Lawrence Steinman, MD, a professor of pediatrics and neurology and neurological sciences at Stanford University School of Medicine, and their colleagues.”

June 22, 2015 – Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System “The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported.”

June 8, 2015 – The narcolepsy-pandemic influenza story: Can the truth ever be unraveled? “(full text) Five years after cessation of the pandemic influenza vaccination campaign we are still left with many questions about the epidemiological association: (1) What is the effect of adjuvanted influenza A (H1N1) pdm09 vaccines on narcolepsy occurrence? For this to be studied the association needs to be studied in parts of the world where awareness in the public and physicians was not widespread and other vaccines were used, this would allow the period of case inclusion to be longer.”

May 5, 2015 – Accounting for personal and professional choices for pandemic influenza vaccination amongst English healthcare workers “The HCWs constructed their receipt of vaccination as a personal choice informed by personal health history and perceptions of vaccine safety, while they viewed patients’ vaccination as choices made following informed consent and medical guidelines. Some HCWs received the A/H1N1 vaccine under the influence of their local practice organizational norms and values. While non-vaccinated HCWs regarded patients’ vaccination as patients’ choice, some vaccinated HCWs saw it also as a public health issue.”

May 5, 2015 – A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy “A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation.”… “Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake.”

April 20, 2015 – The Effect of Reactive School Closure on Community Influenza-Like Illness Counts in the State of Michigan During the 2009 H1N1 Pandemic “In sum, 559 Michigan schools were closed as a nonpharmaceutical intervention during the influenza A 2009 (H1N1) pandemic.”…”These findings suggest that district level reactive school closures were ineffective.” Comment: Of course the findings state ineffective, otherwise the pharmaceutical companies would lose money.

April 16, 2015 – Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?  “To conclude, we highlighted the role of sera cytokine with pro-inflammatory properties and especially interferon-γ being independently associated with narcolepsy close to disease onset. The activity of the interferon-γ network was also increased in the context of narcolepsy after the pandemic flu vaccination being a potential key player in the immune mechanism that triggers narcolepsy and that coordinates the immune response necessary for resolving vaccination assaults.”

April 1, 2015 – Psychiatric Comorbidity and Cognitive Profile in Children with Narcolepsy with or without Association to the H1N1 Influenza Vaccination “In the post-H1N1 vaccination (PHV) narcolepsy group (n = 31), 43% of patients had psychiatric comorbidity, 29% had attention deficit hyperactivity disorder (ADHD) inattentive type, 20% had major depression, 10% had general anxiety disorder, 7% had oppositional defiant disorder (ODD), 3% had pervasive developmental disorder not otherwise specified (i.e., atypical autism), and 3% had eating disorder not otherwise specified (anorectic type). In the non–post-H1N1 vaccination (nPHV) narcolepsy group, one of seven patients had ADHD, inattentive type and ODD. The most frequent psychiatric symptom was temper tantrums, which occurred in 94% of the patients in the PHV group and 71% of the patients in the nPHV narcolepsy group.”

April 2015 – Severity of Influenza A(H1N1) Illness and Emergence of D225G Variant, 2013–14 Influenza Season, Florida, USA “We hypothesize that the emergence of an influenza virus variant bearing the D225G polymorphism enabled the 2013 H1N1 virus to infect lower and upper respiratory tract cells, thereby contributing to the increased severity of the 2013–14 influenza season in our region. Our findings highlight the importance of monitoring genetic changes in the 2013 H1N1 virus to predict the effect of future influenza viruses.”

March 23, 2015 – Description of Hospitalized Cases of Influenza A(H1N1)pdm09 Infection on the Basis of the National Hospitalized-Case Surveillance, 2009–2010, Japan “The overall hospitalization rate was 5.8 cases per 100,000 population when cases hospitalized for non-therapeutic purposes were excluded. While those aged under 20 years accounted for over 85% of hospitalized cases, the largest proportion of fatal cases was observed in those aged over 65 years. The overall case fatality rate for all hospitalized cases was 1.5%.” Comment: Refreshing to see the Japanese Journal of Infectious diseases reports true statistics.

March 9, 2015 – India tackles H1N1 influenza outbreak “Like many other countries, India was affected in the global H1N1 outbreak in 2009 and 2010, which affected 27 236 and 20 604 Indians respectively, resulting in 981 and 1763 deaths.” Comment: India is supposedly a third world country, and it would seem they don’t have as many deaths from the flu as the US. Could the mainstream media be exaggerating the numbers?”

February 2015 – Modeling Receipt of Influenza A(H1N1)pdm09 Vaccinations Among US Children During the 2009–2010 Flu Season: Findings From the 2010 National Health Interview Survey “Conclusions: In the event of future pandemics, public health officials may utilize these findings to target particular segments of the US child population that may have been underserved during the 2009 influenza pandemic.”

January 1, 2015 – Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean “The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious side effects were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious adverse events reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error.”
**Comment: It is interesting that SIX YEARS after the initiation and use of the pandemic H1N1 vaccine, research is still being done on this particular vaccine – and the disasters it left in its wake are still being logged. What was in that vaccine that caused so many deaths and serious side effects? Was it the virus…or some other toxic, unknown “component” that is not mentioned? We will probably never know – but side effects were felt worldwide.

November 6, 2014 – LAIV not effective against influenza A H1N1 viruses in children 2 through 8 years during the 2013-’14 influenza season “Additional data are needed to understand the poor effectiveness of LAIV against influenza A H1N1 viruses during the 2013-’14 season and to determine possible implications for the 2015-’16 influenza season. The CDC and the Academy are exploring the issue of vaccine effectiveness, including working with the manufacturer of LAIV (MedImmune).”…”The LAIV vaccine produced for the 2014-’15 season is unlikely to provide protection against influenza A (H1N1 pdm09), since the same H1N1 vaccine virus was used for production of 2013-’14 vaccine.”

November 2014 – Does autoreactivity have a role in narcolepsy? (full text) “The retraction of the article means that we do not have any clear evidence for molecular mimicry between hypocretin and H1N1 virus. A paucity of evidence, however, does not exclude the possibility that molecular mimicry might be at play in the pathogenesis of H1N1 virus infection-induced narcolepsy. Other non-proteinaceous components of the vaccine might also have an important role.”

October 28, 2014 – Qualitative motivators and barriers to pandemic vs. seasonal influenza vaccination among healthcare workers: A content analysis “HCW vaccination during the pandemic was motivated by panINFLU related fear, epidemiology, and workplace pro-vaccination policies. HCW Perceptions of accelerated panINFLU vaccine development and vaccine safety compromises, negative views of external sources (i.e. media, pharmaceutical companies, and regulatory agencies) and pandemic management strategies were barriers specific to panINFLU vaccine.”

September 16, 2014 – Airway Mucosal Immune-Suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During Pregnancy. “Results: Neonates of mothers vaccinated during pregnancy had significant up-regulation of TGF-[beta]1 (ratio=1.52 [1.22-1.90], p=0.0002), and corresponding down regulation (p<0.05) of IL-12p70, IFN-[gamma], IL-5, eotaxin-1, TARC, MDC, IL-8 in comparison to those vaccinated after pregnancy. The lag-time from vaccination during pregnancy to assessment of the immune signature showed significant and positive association to up-regulation of TGF-[beta]1 levels (P= 0.0003) and significant negative association to other mediators. The incidence of infections in early infancy did not differ between the study groups.” Conclusion: Influenza A(H1N1)pnd09 vaccination during pregnancy up-regulates TGF-[beta]1 and down-regulates key mediators of the protective immunity, but the rate of clinical infections was not detectably affected

August 20, 2014 – Healthcare workers under a mandated H1N1 vaccination policy with employment termination penalty: A survey to assess employee perception “96% felt that the mandating hospital should be liable should a significant adverse effect occur from receiving the vaccine. While the mandate helped to increase HCW influenza vaccination rates dramatically, the strict consequence of employment termination created negative feelings of coercion. Adopting a policy that includes a declination option with mandatory masking during influenza season might be a more widely acceptable and still adequate approach.

August 6, 2014 – A single immunization with inactivated H1N1 influenza vaccine formulated with delta inulin adjuvant (Advax™) overcomes pregnancy-associated immune suppression and enhances passive neonatal protection “We therefore wished to test whether addition of Advax™, a polysaccharide adjuvant based on delta inulin, to an inactivated influenza vaccine (A/H1N1/PR8) administered during pregnancy would safely enhance vaccine immunogenicity and thereby provide improved protection of pregnant mothers and their newborns.”…”This study shows that Advax adjuvant was safe when administered with influenza vaccine during pregnancy and provided protection of pups via enhanced breast milk transfer of anti-influenza antibodies, not seen with administration of unadjuvanted vaccine.” Comment: See more info on the Advax Adjuvant here

July 7, 2014 – The impact of pandemic A(H1N1)pdm09 influenza and vaccine-associated adverse events on parental attitudes and influenza vaccine uptake in young children “Uptake of influenza vaccine decreased significantly from 2010 onwards. From 2010, parents were less concerned about severe influenza, but more concerned about vaccine side effects and safety. Despite this significant shift in attitudes towards influenza vaccine, parental acceptance of vaccines on the national immunisation program did not change. Principal Component Analysis revealed that attitudes around vaccine safety and efficacy were the most important attitudes impacting on vaccine uptake.”

July 1, 2014 – Influenza Vaccine Failure among Highly Vaccinated Military Personal, No protection against Pandemic Strains. “Overall, a low level of protection against clinically-apparent, laboratory-confirmed, influenza was found for the 2010–11 seasonal influenza vaccines. TIV immunization was associated with higher protection than LAIV, however, no protection against A/H1 was noted, despite inclusion of a pandemic influenza strain as a vaccine component for two consecutive years. Vaccine virus mismatch or lower immunogenicity may have contributed to these findings and deserve further examination in controlled studies. Continued assessment of VE in military personnel is essential in order to better inform vaccination policy decisions.

June 19, 2014 – The Ethics of Sharing Preliminary Research Findings During Public Health Emergencies: A Case Study From the 2009 Influenza Pandemic (full text) “The issues outlined here cannot be resolved by merely referring to a theoretical moral duty-to-share or by appealing to professional codes of ethics or legal norms. All of the stakeholders involved need a pathway that accommodates each domain’s needs and constraints. The complexity involved demands a carefully thought-out framework outlining the principles, processes and outcomes that would govern a paradigm shift in the relationship of researchers, funders, scientific journals, public health decision-makers and the public during public health emergencies. Conflicts and communication failures may be minimised if emergency planning includes infrastructure and preparation of all these communities for the conduct of research, its evaluation, dissemination and publication. Alternatively, creating a mechanism that allows for exceptional circumstances, similar to that of the United States Food and Drug Administration (FDA) emergency use authorisation mechanism, or the European Medicines Agency emergency procedures, with well-defined criteria and parameters, may help facilitate more effective communication.

June 11, 2014 – Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 Influenza pandemic (pdf) “Seasonal flu vaccination of children has been reported to interfere with the development of heterosubtypic immunity and Ab responses to pandemic H1N1 appeared to be reduced in participants who received seasonal flu vaccination 3 months prior to vaccination with the pmd flu vaccine. The report by Skowronski and co-workers also suggested an association between the previous 2008–2009 flu vaccination and pandemic H1N1 illness in Canada; the mechanisms underlying this finding are ill-defined and warrant further research to better understand the impact of seasonal flu vaccination , i.e. the potential ‘negative imprint’ of previous vaccinations on cellular immune memory responses.”

June 7, 2014 – Encephalitis related to a H1N1 vaccination: Case report and review of the literature “We report a case of a 26-year-old female who developed symptoms of acute encephalitis 5 days after vaccination against the pandemic 2009 A/H1N1 influenza. MRI of the brain showed confluent T2-hyperintense signal intensity changes in the deep white matter which further confirmed the diagnosis of encephalitis/acute disseminated encephalomyelitis. Despite therapy with immunoglobulins and corticosteroids, her persistent vegetative state continued. In light of the dramatic cause of this case, we reviewed all 21 other previously reported cases of central nervous system demyelination related to H1N1 vaccination and/or infection.” VAERS report

June 2014 – Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination “Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger.”

May 29, 2014 – Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study (full text) “This was a large population based cohort study that investigated the association between the MF59 adjuvanted pandemic A/H1N1 vaccination in pregnancy and multiple adverse outcomes. We did not find an increased risk of either fetal or birth outcomes following vaccination, whereas a limited increase in the prevalence of gestational diabetes and eclampsia was observed.”

May 1, 2014 – Investigation of an Association Between Onset of Narcolepsy and Vaccination with Pandemic Influenza Vaccine, Ireland April 2009-December 2010 (full text) “Our study found a significant, 13.9-fold higher, risk of narcolepsy in children/adolescents vaccinated in Ireland with Pandemrix compared with unvaccinated children/adolescents. The absolute number of narcolepsy cases attributable to Pandemrix vaccination was five per 100,000 vaccinated children/adolescents or one in 19,000 vaccinated (95% CI: 1 in 15,000–1 in 26,000). These findings are remarkably similar to the results found in the retrospective population-based cohort study conducted in Finland in 2011 [12]. This study showed a 12.7 fold higher risk of developing narcolepsy in children/adolescents vaccinated with Pandemrix as compared with unvaccinated children/adolescents. The vaccine attributable risk of developing narcolepsy was one in 16,000 vaccinated 4–19 year-olds (95% CI: 1 in 13,000–1 in 21,000).

May 1, 2014 – Impact of Body Mass Index on Immunogenicity of Pandemic H1N1 Vaccine in Children and Adults “A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to non-obese adults”

May 2014 – A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009–2010 “The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1 antibodies and TRIB2 autoantibody levels particularly among the youngest narcolepsy patients (r = 0.819, p < 0.001).”

April 29, 2014 – Risk factors associated with anaphylaxis and other allergic-like events following receipt of 2009 monovalent AS03-adjuvanted pandemic influenza vaccine in Quebec, Canada “Increased anaphylaxis and other allergic-like events observed in association with AS03-adjuvanted pandemic H1N1 vaccine remain mostly unexplained despite extensive risk factor review. However, prior to mass vaccination with similar formulations this safety signal warrants further consideration and better understanding. In particular, the predominance among women of childbearing age may be a clue to underlying biological or hormonal influences on adverse immunological responses to vaccine.”

April 14, 2014 – The adjuvant component α-tocopherol triggers via modulation of Nrf2 the expression and turnover of hypocretin in vitro and its implication to the development of narcolepsy  “In case of a genetic predisposition (DQB1*602) α-tocopherol could confer to development of narcolepsy by activation of Nrf2 that finally leads to an elevated formation of longer hypocretin-derived fragments that can be presented by HLA-subtype DQB1*602. These cells are recognized by the immune system and due to their increased sensitivity to apoptotic stimuli they can be destroyed, finally leading to a lack of hypocretin.”

April 3, 2014 – Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants (full text) “A/California/07/2009-like virus for the 2013–2014 northern hemisphere winter influenza season as well as for the upcoming 2014 southern hemisphere influenza season and the 2014–2015 northern hemisphere winter influenza season. However, over the past several seasons there have been a number of reports of virus isolates containing amino acid changes in the HA protein that have the potential to alter the antigenic properties of the virus. In this report we observe that the HA protein has accumulated mutations both in total and within the epitope regions that make the potential for vaccine escape highly probable. This has important implications for evolutionary, epidemiological, and clinical aspects of the virus.”

April 2014 – Distribution of Pandemic Influenza Vaccine and Reporting of Doses Administered, New York City, New York, USA (full text) “The results of the survey indicated that a large number of distributed pH1N1 doses were never administered to patients. These results are consistent with other pH1N1 vaccination efforts made in NYC during 2009–2010: only 1 of the 58 weekend point-of-distribution clinics reached capacity, and uptake at the school-located pH1N1 vaccine program was lower than anticipated. As a result, only half of the doses received by DOHMH were administered and nearly all were reported to the CIR. In June 2010, providers who received pH1N1 vaccines from DOHMH were asked to return unused doses to the Central Vaccine Recovery Program operated by the US Department of Health and Human Services. The number of doses returned by NYC providers through this program was reported as 537,538 doses (20% of distributed doses), further supporting the conclusion that a large number of received pH1N1 vaccine doses were never administered.”

March 26, 2014 – Solid Bioneedle-Delivered Influenza Vaccines Are Highly Thermostable and Induce Both Humoral and Cellular Immune Responses (full text) “This study demonstrates the potential of bioneedles as an alternative delivery system for influenza vaccines. The immune responses induced by four influenza vaccine formulations were compared to determine the optimal influenza vaccine for bioneedle vaccine development. All influenza vaccine formulations delivered by bioneedles induced immune responses that were non-inferior to liquid formulations. WIV was determined as the best influenza vaccine formulation for use in bioneedles, due to its ease of formulation and ability to induce both strong humoral and cellular immune responses. The freeze-dried state of the vaccine in the bioneedle makes it suitable for long-term storage outside the cold chain, and enables easy stockpiling.”

February 19, 2014 – Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: What is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants “While a potent immune response would afford children/adolescents protection against infections, it could also paradoxically allow for an easier unmasking of autoimmune disease in the genetically predisposed subject or 2) the role of “germ theory” and repetitive infections in adults that refines the immune response into one that is precisely regulated and specific compared to the more potent and primal immune response from children that provokes autoimmunity when normal tissue is caught in the “cross-fire”. A speculative answer for the second question could be that there is a still-undetermined environmental factor that, along with the HLA susceptibility, triggers narcolepsy.”

January 3, 3014 – Guillain-Barré Syndrome and Adjuvanted Pandemic Influenza A (H1N1) 2009 Vaccines: A Multinational Self-Controlled Case Series in Europe (full text) “Overall, 99 cases (33%) received influenza A(H1N1)pdm09 vaccination, mostly adjuvanted with AS03, before symptom onset (Table 3). Of these, 36 (37%) cases developed GBS within 42 days after a first dose of influenza A(H1N1)pdm09 vaccination whereas 7 cases occurred within the exposure risk window but after a second dose of influenza A(H1N1)pdm09 vaccination.”

• Jeanne P Dieleman has been involved in studies for pharmaceutical companies (i.e., GSK, Sanofi, Astra-Zeneca, Pfizer). None of these had any conflict with the present study.
• The affiliation (i.e. University of Bath) of Corinne S de Vries and Cormac Sammon has research and consulting contracts in place with Novartis vaccines and with GSK pharmaceuticals. The authors do not personally benefit from these contracts; all financial compensation is to the University of Bath and not to the authors
• Terhi Kilpi is a principal investigator of a nationwide Finish effectiveness study of the 10-valent pneumococcal conjugate vaccine, a collaborative study, for which her institute has received funding from GSK.
• Par Sparen received a grant from Glaxo Smith Kline in 2010 to for a retrospective, observational register based cohort study to evaluate the safety of GSK Biological’s H1N1 pandemic vaccine administered in Sweden according to local vaccination policy.
• Miriam CJM Sturkenboom: is head of a research group that occasionally conducts research for pharmaceutical companies including Pfizer, EliLilly, Boehringer, AstraZeneca and Novartis. None was related to this topic.This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

December 19, 2013 – Antibody response to influenza A (H1N1)pdm09 among healthcare personnel receiving trivalent inactivated vaccine: effect of prior monovalent inactivated vaccine “At pre-season (N=1,417) “Conclusions. CP immunization programs should consider effects of host immune-response and vaccine antigenic-distance on immunogenicity of repeated annual doses of influenza vaccines.”

December 19, 2013 – Pandemic influenza A H1N1 vaccines and narcolepsy: vaccine safety surveillance in action “Clinicians in Finland and Sweden later identified an apparent increase in the incidence of narcolepsy associated with a specific adjuvanted pandemic influenza vaccine. After extensive review, the European Medicines Agency confirmed the existence of this association, which has since been detected in England, Ireland, France, and Norway. Assessments of the causal mechanisms continue.”

December 18, 2013 – Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals (full text) “It is unknown if, and to what extent, leptin is correlated with variations in influenza vaccine-induced immune response. It is also unknown if genetic polymorphisms (SNPs) in leptin and leptin-related genes account for the inter-individual variations in immune function among older subjects, increasing or decreasing susceptibility to the development of leptin resistance. The primary objective of this study was to ascertain if genomic and proteomiccorrelations exist between leptin and immune function following influenza A/H1N1 vaccination among older individuals.”

November-December 2013 – Evaluating the Most Effective Distribution Strategies to Assure Administration of Pandemic H1N1 Influenza Vaccine to New York State Children and Adolescents: Evaluation Using the New York State Immunization Information System “Main Outcome Measure(s): Median time to administer vaccines to children and adolescents younger than 19 years by December 31, 2009, by county; venue of H1N1 vaccine administration (local health department[LHD] or private medical provider); comparison of immunization-seeking behavior for routine childhood vaccinations and H1N1 vaccine.”…”Children who always received routine childhood immunizations either within or outside of their county of residence often had the same practice for H1N1 vaccine, with 85% of children following these patterns. Children who did not follow these patterns were more likely to receive H1N1 influenza vaccine through LHD.”

November 14, 2013 – Motor palsies of cranial nerves (excluding VII) after vaccination: Reports to the US Vaccine Adverse Event Reporting System (full text) Cranial nerve palsies were reported after a wide variety of vaccines (Table 3). Most reports (43; 63%) listed a single vaccine. Among reports listing single vaccines, the most common vaccines were influenza vaccine seasonal trivalent inactivated, human papillomavirus vaccine quadrivalent, influenza H1N1 vaccine inactivated, and zoster vaccine live. Among reports listing multiple vaccines, the most common vaccines included hepatitis A vaccine; measles, mumps, and rubella vaccine live; diphtheria and tetanus toxoids and acellular pertussis vaccine; Hemophilus influenzae type b vaccine; and pneumococcal conjugate vaccine 7-valent. There was no conspicuous clustering of live or inactivated vaccines with palsies of particular cranial nerves.

November 11, 2013 – Academics and competing interests in H1N1 influenza media reporting “There is evidence of CoI among academics providing media commentary during the early H1N1 pandemic. Heightened risk assessments, combined with advocacy for pharmaceutical products to counter this risk, may lead to increased public anxiety and demand. Academics should declare, and journalists report, relevant CoI for media interviews.”

November 2013 – Narcolepsy and H1N1 vaccination: a link? “The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility. However, there have not yet been any reports of specific autoimmunity, either antibody or T-cell-mediated.”…”There is a strong association between narcolepsy and H1N1 vaccination. However, whether this reflects a true increase in affected individuals or a hastening of disease onset in individuals who would otherwise have developed narcolepsy later will become clear in the coming years. The pathological explanation of this association and narcolepsy is likely to be autoimmune, although supportive evidence is lacking. Video abstract available: See the Video Supplementary Digital Content 1 (Narcolepsy and H1N1 vaccination: a link?).”

October 31, 2013 – Dramatic Change in Public Attitudes Towards Vaccination During the 2009 Influenza A(H1N1) Pandemic in France “In 2010, we observed a dramatic shift in the French population’s attitudes towards vaccination in general: unfavourable attitudes have become far more frequent, and the corresponding sociodemographic profile has also changed. Such attitudes and sociodemographic profile should be closely monitored in the future, as this shift may either persist or vanish. Moreover, the 2009 influenza A(H1N1) pandemic certainly contributed to this upheaval. As attitudes and behaviours are generally consistent one with another, this phenomenon could have a considerable impact on future vaccination coverage. Consequently, health authorities should urgently address this increasing lack of confidence in vaccination.”

October 19, 2013 – Increased risk of anaphylaxis following administration of 2009 AS03-adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine “A substantial number of patients with early-onset allergic symptoms met the most specific levels of the Brighton case definition but were not reported as anaphylaxis. Based on this specific case definition, the incidence of anaphylaxis after AS03-adjuvanted H1N1pdm09 vaccine substantially exceeded that reported with seasonal influenza vaccines, a signal that warrants better understanding.”

October 12, 2013 – Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: A Phase 1 dose-escalation study in healthy adults (full text)

• Subjects in the study vaccine groups received two doses of HAC1 at 15 μg, 45 μg or 90 μg, administered either non-adjuvanted (Group A [15 μg], Group C [45 μg] and Group E [90 μg]) or with 0.3% aluminum hydroxide (Alhydrogel®) adjuvant (Brenntag Biosector, Denmark) (Group B [15 μg], Group D [45 μg] and Group F [90 μg]).

• “Systemic solicited AEs occurred in 33 subjects (41%), evenly distributed across study groups (Table 2).”

• The most common systemic solicited AE was headache (23 subjects; 29%), which occurred in all study groups with similar incidence ranging from 30 to 50%, except for Group E (90 μg) where no headaches were reported (Table 3). Only four of these headache AEs (5%) were considered vaccine related.
• Unsolicited AEs were more common in all study groups, with 66 subjects (83%) experiencing at least one unsolicited AE (Table 2). Unsolicited AEs had a larger range of intensity, with 15 subjects (19%) experiencing at least one Grade 2 AE, and one subject (1%) experiencing a Grade 3 AE (Table 2).
  
• Four of the unsolicited AEs (5%) were considered vaccine related and all four of these were Grade 1 intensity. The occurrence of unsolicited AEs was similar across all groups following each vaccination.”
• Conflict of interest: Dr. Jacqueline M. Katz has received funding for research not related to the present study from GlaxoSmithKline and Juvaris, Inc. (now Colby Pharmaceuticals).

September-October 2013 – Factors Associated With Receipt of 2009 Pandemic Influenza A (H1N1) Monovalent and Seasonal Influenza Vaccination Among School-Aged Children: Maricopa County, Arizona, 2009-2010 Influenza Season “Context: To target school-aged children (SAC), who were identified as a priority for pandemic 2009 Influenza A (pH1N1) vaccination, Maricopa County (MC) initiated school-based influenza vaccination in 69% of its 706 schools during the 2009-2010 influenza season.”…”Conclusions: Availability of pH1N1 vaccine at school was independently associated with pH1N1 vaccination of MC school-aged children. School-based influenza vaccination campaigns should be considered to increase vaccination among this population.”

September 19, 2013 –A multicenter cohort study of pregnancy outcomes among women with laboratory-confirmed H1N1 influenza “Conclusion: Pregnant women with mild clinical illness secondary to 2009 H1N1 were not at a greater risk of adverse pregnancy outcomes. However, severely infected women were more likely to deliver SGA infants.”

September 16, 2013 – Extended antigen sparing potential of AS03-adjuvanted pandemic H1N1 vaccines in children, and immunological equivalence of two formulations of AS03-adjuvanted H1N1 vaccines: results from two randomised trials (full text) “GlaxoSmithKline Biologicals SA was the funding source and was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also funded all costs associated with the development and the publishing of the present manuscript. The authors had full access to the data and corresponding author was responsible for submission of the publication.

September 1, 2013 – Funding – Awarded Grants Bioinformatics approach to influenza A/H1N1 vaccine immune profiling “Given antigenic drifts during seasonal influenza A infection or large shifts associated with influenza A pandemics, elicitation of antibody-based immunoprotection through vaccination requires continual immunogen modification. Such alterations adversely impact public health preparedness. The current swine flu H1N1 pandemic 2009 strain is a case in point. Here we will use recent advances in bioinformatics and proteomics to explore the potential to elicit protective CDS T cell responses against 153 conserved epitopes derived from 5,315 sets of influenza A taxonomy data covering all internal and surface viral proteins and predicted to bind to common HLA alleles such as HLA-A*0201.”…”Principal investigator: POLAND, GREGORY A. (MAYO CLINIC ROCHESTER )”

August 2013 – Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France “In this sub-analysis,H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.”

July 29, 2013 – Funding – Awarded Grants Protective vaccine for H5N1 Flu using H5 protein and a novel TLR4 agonist “The vaccine antigen is recombinant H5 haemagglutinin (rH5), which uses a production process that simplifies many of the manufacturing issues associated with conventional vaccines, and the adjuvant (GLA-SE) that combines two clinically-validated strategies for augmenting vaccine performance, a synthetic Toll-Like Receptor-4 agonist, GLA, and an oil-in-water emulsion, SE.”…”The US and world governments are investing billions of dollars in pandemic preparedness measures and TRIA will be well-positioned to participate in this market. This vaccine’s design is broadly applicable to other infectious diseases, which increases its commercial potential Awarded grant: 1,000,000 USD Principal investigator: POLAND, GREGORY A. | Sponsor: National Institute of Allergy and Infectious Diseases”

July 12, 2013 – Long-term immunogenicity of an AS03-adjuvanted influenza A (H1N1)pdm09 vaccine in young and elderly adults: An observer-blind, randomized trial (full text) “This large-scale, randomized study in subjects ≥18 years of age assessed whether one dose of AS03-adjuvanted 3.75 μg HA influenza A (H1N1)pdm09 vaccine elicited immune response that met the US and European regulatory criteria. Additionally, non-inferiority and superiority of this vaccine protective efficacy versus a non-adjuvanted 15 μg HA influenza A (H1N1)pdm09 vaccine were evaluated.”…”Two of these events, intestinal obstruction (AS03-adjuvanted treatment group) and multiple sclerosis (non-adjuvanted treatment group) were considered by the investigator to be possibly related to study vaccine and were also considered pIMDs. Through Day 385 (Month 12), 12 pIMDs according to the predefined list of pIMD preferred terms were reported, with 5 and 7 in AS03-adjuvanted and non-adjuvanted influenza treatment groups, respectively. Seven fatal SAEs were reported, 6 and 1 in AS03-adjuvanted and non-adjuvanted treatment groups, respectively. All were assessed by investigators as not related to vaccination.”…”All investigators received compensation for study involvement and travel related to this study. Ping Li, Miguel Madariaga, Olivier Godeaux and David Vaughn are/were employees of GlaxoSmithKline group of companies and report receiving restricted shares of the company. Contributorship: W.Y., M.D., M.K. and N.A. contributed to the data collection, data interpretation and critical review of the manuscript drafts. P.L., M.M., O.G. and D.W.V. contributed to the study design, data analysis and interpretation as well as to the critical review of all drafts of the manuscript. Trade mark statement: Arepanrix is a trade mark of GlaxoSmithKline group of companies.”

July 8, 2013 – Influenza vaccination coverage rates among adults before and after the 2009 influenza pandemic and the reasons for non-vaccination in Beijing, China: A cross-sectional study (full text) “A higher level of education is usually thought to be positively associated with vaccination uptake; however, we found that a low level of education had a positive impact on the influenza vaccination uptake. In the current study, illiterate respondents were less likely to indicate that they did not expect to contract influenza compared to those reporting higher levels of education. Second, media broadcasts and internet discussions have fueled social suspicion about the safety and effectiveness of influenza vaccination.”

May 6, 2013 – Chart-Confirmed Guillain-Barré Syndrome After 2009 H1N1 Influenza Vaccination Among the Medicare Population, 2009–2010 “Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1–119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination”

May 2, 2013 – Scientists create hybrid flu that can go airborne “A team of scientists in China has created hybrid viruses by mixing genes from H5N1 and the H1N1 strain behind the 2009 swine flu pandemic, and showed that some of the hybrids can spread through the air between guinea pigs. The results are published in Science. Flu hybrids can arise naturally when two viral strains infect the same cell and exchange genes. This process, known as reassortment, produced the strains responsible for at least three past flu pandemics, including the one in 2009. Comment: It becomes more obvious all the time that scientists are intentionally manipulating the genes of influenza viruses to make them more easily spread and more deadly. Is this to cause the Global pandemic the Powers That Be have been predicting – even creating – for the last several decades? Or this a way to make sure every human on the planet is injected with the contents of a flu vaccine?

April 18, 2013 – Altered Response to A(H1N1)pnd09 Vaccination in Pregnant Women: A Single Blinded Randomized Controlled Trial “Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women.”… “TFT is employed by Novartis Vaccines. The nested vaccine study is funded by Novartis Vaccines and Diagnostics GmbH, Marburg, Germany, who provided vaccines and funding as an unrestricted institutional grant.”

April 17, 2013 – New Wisdom to Defy an Old Enemy: Summary from a scientific symposium at the 4th Influenza Vaccines for the World (IVW) 2012 Congress, 11 October, Valencia, Spain (full text) “The developing fields of systems biology, vaccinomics, and predictive vaccinology may aid in the prediction of an individual’s response to a vaccine, both in terms of efficacy and adverse events, and will allow an increasingly individualized vaccine approach.”…”However, experimental strategies for improved vaccine performance also carry risks of increased side effects or adverse events. In addition, because most of these approaches lack previous large-scale human experience, many new vaccine candidates also carry a risk of rare but potentially serious adverse events. The recent report of increased incidence of narcolepsy following the distribution and utilization of AS03-adjuvanted pandemic H1N1 vaccine may represent such a risk.

April 2013 – “Trivalent influenza vaccination of healthy adults 3 years after the onset of swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v constituent?” “Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.”

April 2013 – Unusual Patterns of IgG Avidity in Some Young Children following Two Doses of the Adjuvanted Pandemic H1N1 (2009) Influenza Virus Vaccine “Although the antibody titers were similar, some antigen-naive children demonstrated an unusual pattern of avidity maturation after two immunizations with AS03-adjuvanted, low-dose influenza virus vaccine.These data suggest the presence of subtle differences in the quality of the antibodies produced by some subjects in response to this vaccine.”

April 2013 – Long-Term Immunogenicity of the Pandemic Influenza A/H1N1 2009 Vaccine among Health Care Workers: Influence of Prior Seasonal Influenza Vaccination “In conclusion, HCWs should be encouraged to receive an annual influenza vaccination, considering the risk of repeated exposure. However, prior reception of seasonal influenza vaccine showed a negative influence on immunogenicity for the pandemic A/H1N1 2009 influenza vaccine.

March 27, 2013 – Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation (full text) “Although exit screening is more efficient than entry screening, significant political, legal and practical obstacles often hamper the timely and effective implementation of national strategies for exit screening. Currently, most national quarantine authorities are structured to prevent the import of pathogens but not their export. Similarly, the customs and passport control infrastructures at most international airports – which could be used as the basis of a health screening programme – are focused on arrivals rather than departures. Furthermore, at least in the short-term, the benefits of exit screening in any country with an epidemic would be realized entirely by other countries while placing additional strain on the source country.”

March 26, 2013 – Evaluation of In Vitro Cross-Reactivity to Avian H5N1 and Pandemic H1N1 2009 Influenza Following Prime Boost Regimens of Seasonal Influenza Vaccination in Healthy Human Subjects: A Randomised Trial (full text) “This study was supported by MedImmune, which also provided FluMist Seasonal Trivalent Live Attenuated Intranasal Vaccine for use in the trial. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. There are no patents, products in development or marketed products to declare.”

March 13, 2013 – Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis “The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a person’s own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome.” Found 626 events where Vaccine is FLU or FLU(H1N1) or FLUN or FLUN(H1N1) and Symptom is Guillain-Barre syndrome and Vaccination Date from ‘2009-01-01’ to ‘2013-12-31’ – Before Found 74 cases where Vaccine is FLUN(H1N1) or FLUX(H1N1) and Symptom is Guillain-Barre syndrome

March 2013 – The 2009 influenza pandemic “To count deaths is one of epidemiology’s oldest pursuits. However, accurate counting of the number of deaths caused by influenza remains an elusive goal, partly because the infection is short-lived, manifests in non-specific ways that only laboratory tests can confirm, and is often treated no differently to the many other clinically indistinguishable influenza-like illnesses. The problem is compounded by the absence of surveillance systems, even in the highest-income countries, that can accurately quantify the proportion of influenza-like illness that is due to influenza viruses—an essential number to ascertain if the impact of influenza is to ever be measured accurately.

February 26, 2013 – Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis “In conclusion, we found evidence of an increased risk of narcolepsy in children who received pandemic A/H1N1 2009 influenza vaccine (Pandemrix) in England. Despite attempts to minimise ascertainment bias, the potential for overestimation of risk remains because of more rapid referral of vaccinated patients. Long term follow-up of the cohorts exposed to the vaccine is needed to properly evaluate the attributable risk. As a precaution, based on the preliminary reports from Sweden and Finland and pending the outcome of confirmatory studies, in July 2011 the European Medicines Agency changed the indication for use of Pandemrix vaccine in people aged under 20 to those for whom seasonal trivalent vaccine was not available and for whom prevention of A/H1N1 2009 influenza was considered necessary. Its licence, however, remains valid, and the vaccine can still be manufactured and sold in any European Union country.”

February 6, 2013 – The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns “The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.”

January 23, 2013 – Vaccination against pandemic A/H1N1 2009 influenza in pregnancy and risk of fetal death: cohort study in Denmark “Based upon your statement, please provide a table of the Gestational Week, ranging from 0 to 43 weeks, then a column of vaccinated and unvaccinated showing the total number of pregnancies and fetal loses for each group (vaccinated and unvaccinated).”

January 22, 2013 – Effectiveness of Monovalent A(H1N1)pdm09 and 2010-11 Trivalent Inactivated Influenza Vaccines in Wisconsin During the 2010-11 Season “Monovalent vaccine provided no sustained protection against A(H1N1)pdm09 during the 2010-11 season. This waning effectiveness supports the need for annual revaccination, even in the absence of antigenic drift.”

December 15, 2012 – 2009 Pandemic Influenza A Virus Subtype H1N1 Vaccination in Africa—Successes and Challenges “From February through November 2010, 32.2 million doses were delivered to 34 countries in Africa. Of the 19.2 million doses delivered to countries that reported their vaccination activities to WHO, 12.2 million doses (64%) were administered. Population coverage in these countries varied from 0.4% to 11%, with a median coverage of 4%. All countries targeted pregnant women (median proportion of all vaccine doses administered [mpv], 21% [range, 4%–72%]) and healthcare workers (mpv, 9% [range, 1%–73%]).”

December 13, 2012 – Impact of preexisting memory to seasonal A/H1N1 influenza virus on the immune response following vaccination against avian A/H5N1 virus “Here we show that under resting conditions about45% of human adults never vaccinated nor exposed to avian A/H5N1 influenza have detectable circulating MBCs cross-reacting with H5N1. This proportion rises to 63.3% among subjects with a large pool of MBCs specific for seasonal H1N1 (i.e. frequency ≥1% of total IgG MBCs).”

December 7, 2012 – Scientists and policy makers gathered in the post H1N1 pandemic period at the Fourth ESWI Influenza Conference “To cope with a future pandemic outbreak of influenza, heightened readiness is needed on a global scale. Global monitoring of human and animal influenza must be improved to evaluate the spread of existing influenza viruses and to detect the appearance of new influenza virus strains. Such improved monitoring relies on effective surveillance that also covers the current white spots on the world map. Current pre-pandemic vaccines must be tested for effectiveness against the emerging mutant influenza virus strains. Investments in studies on the evolution of influenza viruses in humans and animals must be increased to better understand the evolution of influenza viruses.”

November 2012 – Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil (full text) “Another limitation was the lack of classification of the severity of the AEFI. The outcomes that were considered serious (i.e., death, hospitalisation and permanent or temporary disability) were monitored; however, the reported signs and symptoms were not classified according to their intensity, as the interviews were made by telephone and physical examinations were not performed.”

October 9, 2012 – Toward unbiased assessment of treatment and prevention: modeling household transmission of pandemic influenza (pdf) “House and colleagues jointly estimated the transmission probability and the diagnostic performance parameters of differential case definitions to better integrate all the epidemiological data available. Achieving such joint estimation will eventually permit us to precisely estimate the efficacy of antiviral treatments and vaccination without suffering from ascertainment bias.”

October 5, 2012 – A prospective observational safety study on MF59® adjuvanted cell culture-derived vaccine, Celtura® during the A/H1N1 (2009) influenza pandemic “Overall, 7348 AEs were reported in 2296 of 3989 enrolled subjects (57.6%). Only two AEs were considered related to injection site reactions. No laboratory-confirmed cases of influenza were reported. There were 108 medically confirmed serious adverse events (SAEs) reported among 73 subjects with 6 such SAEs described as possibly or probably related to vaccination. Three fatal cases were reported and assessed as not related to vaccination. Two AESIs classified as convulsion were reported and assessed as not related to vaccination. Both AESIs occurred well outside the pre-specified 7 day risk window representing the likely timeframe of the occurrence of seizure following vaccination.”

October 2012 – Laboratory-Confirmed Pandemic H1N1 Influenza in Hospitalized Adults: Findings from the Canadian Nosocomial Infections Surveillance Program, 2009–2010 “The incidence of pH1N1 influenza was 2.08 cases per 1,000 patient admissions.”

September 24, 2012 – ECDC studies shed new light on narcolepsy and H1N1 vaccine “The full 159-page report and a summary of the findings are available on the ECDC’s Web page. Only one vaccine has been linked to the narcolepsy cases, Pandemrix, made by GlaxoSmithKline, which contains the company’s proprietary AS03 adjuvant.”

September 1, 2012 – Editorial Commentary: Seasonal Influenza Vaccines During the 2009 Pandemic: Help or Harm? “Neutralizing antibodies at likely protective levels were found in older individuals, which predicted the protection seen during the pandemic. No such antibody was found in young children and even after receiving seasonal vaccine they showed no cross-reactive response to the pandemic virus.”

September 2012 – Seasonal and H1N1 influenza vaccine compliance and intent to be vaccinated among emergency medical services personnel “EMT-targeted interventions should be used to increase vaccine compliance, including implementing a mandatory vaccination policy and addressing EMTs’ beliefs and attitudes about vaccine in an education campaign.”

September 2012 – Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study “Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study “Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics.”

September 2012 – Narcolepsy in association with pandemic influenza vaccination (pdf) “A total of 249 cases with verified narcolepsy were submitted (135 from non-signalling countries). A total of 152/249 cases entered the primary analysis (MSLT referral date during April 2009–30 June 2010) (signalling/non-signalling: 63/89). Of those 152 cases, 88 were children/adolescents (signalling/nonsignalling: 44/44) and 64 adults (signalling/non-signalling: 19/45).”

August 17, 2012 – Failure of the vaccination campaign against A(H1N1) influenza in pregnant women in France: Results from a national survey “The vaccination campaign resulted in poor vaccination coverage, strong social inequalities, and no special protection for pregnant women at the highest risk of complications. These findings provide essential information for the organization of future vaccination campaigns.”

July 11, 2012 – Risk of Guillain-Barré Syndrome Following H1N1 Influenza Vaccination in Quebec (full text) “In Quebec, a cluster of GBS cases was observed shortly after the start of the mass immunization campaign using an ASO3 adjuvant 2009 influenza A(H1N1) vaccine. Two different methods were used to assess the risk associated with vaccine administration, and different definitions were applied for GBS cases and the postvaccination risk period. All RR estimates were greater than 1 and statistically significant for the 4-week postvaccination period. The excess risk was observed only in persons aged 50 years or older. The number of cases attributable to vaccination was approximately 2 per 1 million doses.”… Conflicts of Interest. Dr De Wals reports receiving research grants, honoraria, and reimbursements of travel expenses from vaccine manufacturers including GlaxoSmithKline, Novartis, Sanofi Pasteur, Merck, and Pfizer. Ms Boulianne reports receiving research grants from Sanofi Pasteur and GlaxoSmithKline. Dr De Serres reports receiving research grants from Sanofi Pasteur and GlaxoSmithKline. No other disclosures were reported.”

July 2012 – Dose-range Study of MF59-adjuvanted Versus Nonadjuvanted Monovalent A/H1N1 Pandemic Influenza Vaccine in Six- to Less Than Thirty-Six-month-old Children (full text) “Supported by a research grant provided by Novartis Vaccines and Diagnostics (to S.L.B.). This project has been funded in whole or in part with Federal funds from the Office of Public Health Emergency Preparedness, Office of Research and Development Coordination, under Contract Number HHSO100200700030C.J.B, V.S and S.J.H are permanent employees of Novartis Vaccines and Diagnostics. The authors have no other funding or conflicts of interest to disclose.”

July 2012 – Cost Comparison of 2 Mass Vaccination Campaigns Against Influenza A H1N1 in New York City “The school campaign delivered approximately 202 089 vaccines for $17.9 million and $88 per dose. The delivered 49 986 vaccines for community campaign$7.6 million and $151 per dose. At projected capacity, the school campaign could have delivered 371 827 doses at $53 each or $13 each when we excluded the value of in-kind resources. The community points of dispensing could have administered 174 000 doses at $51 each or $24 each when we excluded the value of in-kind resources.

June 20, 2012 – The potential effect of temporary immunity as a result of bias associated with healthy users and social determinants on observations of influenza vaccine effectiveness; could unmeasured confounding explain observed links between seasonal influenza vaccine and pandemic H1N1 infection? (pdf) “It is worth also noting that winter regularly brings a mixture of different influenza and other respiratory viruses. If it is true that the activation of temporary immunity by one respiratory virus might affect susceptibility to others, then this effect may operate to a greater or lesser extent during every influenza season, and would also be likely to vary during any given season. Given the relationship between respiratory infections and vaccination, there is significant potential for this to be an important contributor to unexplained variation in observed vaccine effectiveness.”

June 17, 2012 – Volume of print media coverage and diagnostic testing for influenza A(H1N1)pdm09 virus during the early phase of the 2009 pandemic “A positive correlation (r = 0.67; p = 0.02) was seen between the volume of school-related articles and the number of laboratory-confirmed cases. Increased testing during the most intense period of the pandemic was mainly seen in school-aged children (5–15 years) and adults (≥16 years). Adults accounted for the highest number of tests, but had the lowest positivity rates, which were highest among school-aged children. As the volume of media coverage decreased this was followed one week later by a fall in the number of tests and positivity rates in each age-group.”

June 8, 2012 –  Enhancing the reproducibility of serological methods used to evaluate immunogenicity of pandemic H1N1 influenza vaccines—An effective EU regulatory approach “Haemagglutination-inhibition (HI) and virus neutralisation (VN) assays are routinely applied to evaluate influenza vaccine immunogenicity for regulatory approval. Despite their frequent use, both assays are poorly standardized causing considerable inter-laboratory variation of serological results that is particularly evident for pandemic influenza vaccines.” Comment: Immunogenicity means the ability of the immune system to create an antibody. The tests are poorly standardized, making the ability to compare the results and “effectiveness” of H1N1, pandemic vaccines.

June 5, 2012 – Seasonal Influenza Vaccines During the 2009 Pandemic: Help or Harm? “Antibody determinations only partially predict protection, so clinical studies with virus identification are still necessary. Randomized clinical trials are the reference standard for examining vaccine efficacy but can be carried out only under special circumstances, given costs and logistical considerations.

June 1, 2012 – Risk of Confirmed Guillain-Barré Syndrome Following Receipt of Monovalent Inactivated Influenza A (H1N1) and Seasonal Influenza Vaccines in the Vaccine Safety Datalink Project, 2009–2010 “1–42 days following TIV-only vaccination versus 43–84 days following vaccination (risk difference = 1.1 cases per million doses, 95% confidence interval: −3.1, 5.4). Further evaluation to assess GBS risk following both vaccination and respiratory infection is warranted.”

May 2012 – Comparison of the Adverse Events Associated with MF59-Adjuvanted and Non-Adjuvanted H1N1 Vaccines in Healthy Young Male Korean Soldiers. “Atopic dermatitis (adjusted OR [aOR], 2.32; 95% CI, 0.99-5.46) might be the choice risk factor for local adverse events, and adjuvant use (aOR, 1.35; 95% CI, 1.03-1.78) was a significant predictor of systemic adverse events in healthy young male Korean soldiers.”

March 24, 2012 – A cluster of nonspecific adverse events in a military reserve unit following pandemic influenza A (H1N1) 2009 vaccination—Possible stimulated reporting? ” We investigated a cluster of nonspecific AE in an Army Reserve unit after inactivated pandemic 2009 (H1N1) vaccine. ► We reviewed VAERS reports and hospital records and surveyed reservists. ► AE following the vaccine were more often reported by female and black reservists. ► This cluster represents possible stimulated reporting of AEs among service personnel.”

March 21, 2012 – 2009 H1N1: risk factors for hospitalization in a matched case-control study “Controls were patients aged 6 months to 18 years with confirmed 2009 influenza A (H1N1) infection managed on an outpatient basis. There were 195 cases and 184 controls. In a multivariate model, hospitalization was more frequent in children aged <2 years (odds ratio (OR), 13.8; 95% confidence interval (CI), 1.7–106.4), those with neurological and/or neuromuscular diseases (OR, 3.0; 95% CI, 1.1–8.2), (OR, 2.7; 95% CI, 1.4–5.2). Children aged <2 years, children with neurological diseases, and those whose parents had less than a secondary educational level children from families with a lower educational status had a higher risk of hospitalization due to influenza A (H1N1) 2009 infection.” Comment: The abstract does not mention if children with influenza had been vaccinated prior to being followed either as an outpatient or if those who had been vaccinated were more (or less) likely to be admitted to the hospital.

March 9, 2012 – The reporting completeness of a passive safety surveillance system for pandemic (H1N1) 2009 vaccines: A capture–recapture analysis “The estimated-to-expected ratio for Bell’s palsy in the interval 0–42 days after vaccination was 1.48 (95% CI 1.11–1.98). Reporting completeness was higher for GBS than other adverse events after 2009 H1N1 vaccination. Linking the NADRRS to existing data sources in a capture–recapture analysis can be considered as an alternative to enhance Taiwan’s postlicensure safety assessment of other routine vaccines. Nevertheless, the possibility of an increased risk for Bell’s palsy detected by capture–recapture analyses needs further evaluation by controlled studies.”

February 6, 2012 – Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009–10 (full text)

January 25, 2012 – Notice to Readers: Revised Estimates of the Public Health Impact of 2009 Pandemic Influenza A (H1N1) Vaccination  (full text) “As a result of a programming error, the model used to estimate the impact of vaccination did not adequately adjust for the decreasing risk for disease as the pandemic progressed, and thus the impact of vaccination was overestimated.”

January 25, 2012 – Effectiveness of vaccine against pandemic influenza A/H1N1 among people with underlying chronic diseases: cohort study, Denmark, 2009-10 (full text) “An increased risk of laboratory confirmed H1N1 infection was observed during the first 1-7 days after receiving the pandemic vaccine, with vaccine effectiveness estimates of −112% (95% confidence interval −187% to −56%) compared with those who did not receive either the pandemic or the seasonal influenza vaccines. In the following 8-14 days, no significant effectiveness from the pandemic vaccine was observed, and effectiveness was 49% (10% to 71%) more than 14 days after receiving the vaccine  Those who received only the 2009-10 seasonal influenza vaccine had an increased risk of laboratory confirmed H1N1 infection compared with those who were not vaccinated (hazard ratio 2.31, 95% confidence interval 1.65 to 3.23).”

January 24, 2012 – Seroprevalence of antibodies to the influenza A (H1N1) virus among healthcare workers prior to the 2009 pandemic peak. “Around 25% of healthcare workers in our hospital had positive serology before the peak of the pandemic, none of them had received vaccine for Influenza A (H1N1) 2009 or had been diagnosed of influenza previously.”

January 21, 2012 – The Food and Drug Administration’s Post-Licensure Rapid Immunization Safety Monitoring program: strengthening the federal vaccine safety enterprise. “PRISM has now been integrated into the FDA’s Mini-Sentinel pilot program. It strengthens the federal vaccine safety enterprise in two important ways. First, PRISM monitors the largest US general population cohort designated for active surveillance of vaccine safety. Second, PRISM links data from health plans with data from state and city immunization registries, which were a crucial source of exposure data in the H1N1 vaccine evaluation.”

October 6, 2011 – Seasonal influenza vaccination predicts pandemic H1N1 vaccination uptake among healthcare workers in three countries “The acceptance of pandemic vaccine among healthcare workers was poor (13–41% of respondents). Breaking barriers to accept seasonal influenza vaccination should be part of the influenza pandemic preparedness plan. Mandatory vaccination even during pandemic is likely to arouse substantial discontent.”

October 2011 – Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination. “The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.”

September 16, 2011 – Atraumatic osteonecrosis of the humeral head after influenza A-(H1N1) v-2009 vaccination “Although the available data cannot establish a causal relationship, our patient’s clinical course – with a continuous transition from increased local post-vaccination reactions to symptoms of a severe shoulder lesion with osteonecrosis – raises the question of a pathogenetic link. Considering the vascular pathogenesis of osteonecrosis, we hypothesize that our patient’s enhanced local immunologic reaction may have led to regional vasculitis as the cause of bone destruction.

August 26, 2011 – Coverage and side effects of influenza A(H1N1) 2009 monovalent vaccine among primary health care workers “The low vaccination rate in this study is consistent with previous studies done in many parts of the world and in Spain. Further studies should be done to explore the factors that hindered the uptake and resistance of HCWs to vaccination to H1N1 vaccine.”

July 2011 – Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population “A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.”

June 10, 2011 – Phosphatidylglycerol Suppresses Influenza A Virus Infection “The lipid also suppressed viral attachment to the plasma membrane and subsequent replication in MDCK cells. Two virus strains, H1N1-PR8-IAV and H3N2-IAV bind to POPG with high affinity but exhibit only low affinity interactions with the structurally related lipid palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed the development of inflammatory cell infiltrates and the induction of IFN- recovered in bronchoalveolar lavage, and viral titers recovered from the lungs after 5 days of infection. These findings identify supplementary POPG as a potentially important new approach for treatment of IAV infections.”

May 17, 2011 – Ischaemic stroke and influenza A H1N1 vaccination: a case report. (full text) “Neurological deficit was found 7 h after influenza A/H1N1 vaccination in our patient. However, the exact time of onset is actually unknown as he fell asleep unusually for 5 h. The causal relation between vaccination and ischaemic stroke is seriously challenged, similar to previous reports, especially when our patient does have a few stroke risk factors, such as hypertension, previous stroke, intracranial atherosclerosis, old age, and hypertriglyceridaemia. Our patient’s infarction is compatible with small- to medium-size artery occlusion which is also seen in other ischaemic stroke patients after vaccination or vaccination-related angiopathy.

January 2011 – Adverse neurologic reactions after both doses of pandemic H1N1 influenza vaccine with optic neuritis and demyelination. “We report an unusual case in which neurologic signs occurred in a previously healthy child after both doses of H1N1 2009 influenza vaccine, culminating in bilateral optic neuritis and disseminated encephalomyelitis. A causal association is more likely with repeated injury following influenza vaccination.”

Volume 4 Number 3, 2011 – Acute transverse myelitis following vaccination against H1N1 influenza: a case report (pdf) “Transverse myelitis has been reported previously to occur after vaccination However, there is no report of transverse myelitis occurring after immunization with H1N1 influenza vaccine. We thought it worthwhile to present this case and raise the concern to the potential severe adverse events although it is very difficult to confirm or exclude the possible relevance between the vaccination and occurrence of the myelitis since idiopathic myelitis and a number of other common diseases of children may occur coincidentally after vaccinations.

December 5, 2010 – Rhabdomyolysis secondary to influenza A H1N1 vaccine resulting in acute kidney injury “We describe a case of a man who had been using statins and developed rhabdomyolysis the day after influenza A H1N1 vaccination. A 58-year-old man was admitted at the emergency room complaining of impaired gait. The patient reported receiving influenza A H1N1 vaccine 5 days prior to the admission, with symptoms beginning the day after the inoculation.”

November 2010 – Historical thoughts on influenza viral ecosystems, or behold a pale horse, dead dogs, failing fowl, and sick swine “Unstable gene constellations found in avian species become stable viruses only upon switching to secondary hosts, but may then adapt and circulate independently. It may be desirable to think of influenza A viruses as existing and evolving in a large ecosystem involving multiple hosts and environments. Implications for understanding human influenza are discusssed.

August 2010 – Longitudinally Extensive Transverse Myelitis Following Vaccination With Nasal Attenuated Novel Influenza A(H1N1) Vaccine (full text) “The negative serology results coupled with the negative bacterial, viral, and fungal culture results on the cerebrospinal fluid excluded the possibility of an infectious cause. There was no laboratory evidence of vasculitis or connective tissue disease. Having effectively eliminated the most probable causes for this patient’s condition, we attributed it to postvaccination TM following novel influenza A(H1N1) vaccination.”

March-April 2010 – Using an H1N1 vaccination drive-through to introduce healthcare students and their faculty to disaster medicine. “Recent and past events, here and abroad, have demonstrated that in times of great healthcare need, professional students, through either volunteerism or impressments, have been an important asset in disaster medicine and mass gatherings. The current H1N1 situation affords healthcare educators an opportunity to expose the current generation of students to disaster medicine and management of care for aggregates and populations.”

July/August 2010 – Prevalence of Antibodies Associated with Herd Immunity: A New Indicator to Evaluate the Establishment of Herd Immunity and to Decide Immunization Strategies “Results. The herd immunity was not established (p < pc) against measles, mumps, and varicella in schoolchildren aged 6 to 9 years, against measles in individuals aged 15 to 24 years, and against pertussis in all age groups. Based on these results, the measles-mumps-rubella (MMR) vaccine should be given to schoolchildren and individuals aged 15 to 24 years, the varicella vaccine to schoolchildren aged 6 to 9 years, and the diphtheria-tetanus-pertussis (DTaP/dTaP) vaccine to all age groups in order to establish the necessary herd immunity in the population.”

May 18, 2010 – Guillain-Barré Syndrome Following H1N1 Immunization in a Pediatric Patient (full text) “An 11-year-old boy was admitted to the hospital after onset of facial diplegia, as well as acute cervical, forehead, abdominal, and thigh pain. He had received the Arepanrix H1N1 vaccine (lot 343AA), a monovalent H1N1 vaccine containing an adjuvant manufactured by GlaxoSmithKline. The 0.5-mL dose was injected intramuscularly. On day 13 following administration of the Arepanrix vaccine, his symptoms began and were confined primarily to headaches and cervical pain, which was increasing in intensity, as well as nausea and daily vomiting. On day 14, the patient presented a transitory paresthesia of the fingers and toes, then very pronounced pain in his legs and less pronounced pain in his arms, along with mobility problems. He did not at that time experience definite weakness nor did he exhibit ataxia.” Guillain-Barre_Syndrome_Following_H1N1_Immunizatio

April 2, 2010 – Interim Results: Influenza A (H1N1) 2009 Monovalent and Seasonal Influenza Vaccination Coverage Among Health-Care Personnel — United States, August 2009–January 2010“To further assess strategies for increasing vaccination coverage among HCP, longitudinal surveillance of seasonal influenza vaccination among HCP was initiated through CDC’s National Healthcare Safety Network (NHSN)**** in September 2009. Enrolled health-care facilities are able to enter yearly individual-level vaccination data, including statements of declination among facilities opting for mandatory influenza vaccination. With increases in enrollment, NHSN might be able to provide national estimates for yearly vaccine coverage among HCP, identify undervaccinated HCP groups, and target appropriate interventions to increase coverage.”

November 19, 2009 – Mandatory Vaccination of Health Care Workers (full text) “Many health care workers believe that the mandate violates fundamental individual rights and public health policy, and some have filed court actions. In response, one judge ordered a delay in implementing the regulation, and New York’s governor, David Paterson, suspended the requirement so that the limited supply of H1N1 vaccine currently available can be distributed to the populations most at risk for serious illness and death.”

November 12, 2009 – Swine Flu and the risk of vaccination in allergic patients (pdf) “The EU law authorizes a maximum of 1 microgram of egg albumin per vaccine. In theory this quantity does not present a danger to individuals allergic to egg. “However, EAACI recommends that those individuals whose allergy is proven, special precautions consisting of vaccination in a safe environment should be taken,” underlines Prof. Paolo Rossi from Rome, member of the Board of EAACI Section of Pediatrics. In general, only those patients with a confirmed or suspected allergy to egg ovalbumin and are on a 100 percent egg-free diet, need to be sent to an allergy specialist for vaccination.

November 2009 – Possible hidden hazards of mass vaccination against new influenza A/H1N1: have the cardiovascular risks been adequately weighed? “Evidence from animal experiments in conjunction with clinical epidemiological data indicates that, quite irrespective of cause, stimulation of the immune system may accelerate atherogenesis. Application of adjuvanted flu vaccines to individuals at risk may therefore aggravate the course of underlying atherosclerotic vessel disease with all the clinical consequences. The same may hold true for other widespread diseases that are propelled by deregulated immune mechanisms. Safety trials conducted to date have not specifically taken these possible side effects into account, and unexpected serious adverse effects thus may follow in the wake of a general vaccination program.”

October 24, 2009 – Declaration of a National Emergency with Respect to the 2009 H1N1 Influenza Pandemic by the President of the United States of America – a Proclamation (pdf) “On April 26, 2009, the Secretary of Health and Human Services (the “Secretary”) first declared a public health emergency under section 319 of the Public Health Service Act, 42 U.S.C. 247d, in response to the 2009 H1N1 influenza virus. The Secretary has renewed that declaration twice, on July 24, 2009, and October 1, 2009.”

October 2009 – H1N1 Influenza in Pregnancy Cause for Concern (pdf) “Venous thromboembolic events have also been noted in other case reports and deserve special attention in the pregnant and postpartum critically ill patient as physiologic hypercoagulability compounded by immobilization predisposes these patients to this complication.”

December 2008 – Influenza vaccination of healthcare workers, oseltamivir resistance and prepandemic vaccination (full text) “The main topics discussed were the possible mandatory vaccination of healthcare workers against seasonal influenza, the oseltamivir resistance, the pandemic and prepandemic vaccination strategies a